Innate and adaptive immunity interact to quench microbiome flagellar motility in the gut

Tyler C. Cullender, Benoit Chassaing, Anders Janzon, Krithika Kumar, Catherine E. Muller, Jeffrey J. Werner, Largus T. Angenent, M. Elizabeth Bell, Anthony G. Hay, Daniel A. Peterson, Jens Walter, Matam Vijay-Kumar, Andrew T. Gewirtz, Ruth E. Ley

Research output: Contribution to journalArticlepeer-review

191 Scopus citations

Abstract

Gut mucosal barrier breakdown and inflammation have been associated with high levels of flagellin, the principal bacterial flagellar protein. Although several gut commensals can produce flagella, flagellin levels are low in the healthy gut, suggesting the existence of control mechanisms. We find that mice lacking the flagellin receptor Toll-like receptor 5 (TLR5) exhibit a profound loss of flagellin-specific immunoglobulins (Igs) despite higher total Ig levels in the gut. Ribotyping of IgA-coated cecal microbiota showed Proteobacteria evading antibody coating in the TLR5-/- gut. A diversity of microbiome members overexpressed flagellar genes in the TLR5-/- host. Proteobacteria and Firmicutes penetrated small intestinal villi, and flagellated bacteria breached the colonic mucosal barrier. In vitro, flagellin-specific Ig inhibited bacterial motility and downregulated flagellar gene expression. Thus, innate-immunity-directed development of flagellin-specific adaptive immune responses can modulate the microbiome's production of flagella in a three-way interaction that helps to maintain mucosal barrier integrity and homeostasis.

Original languageEnglish (US)
Pages (from-to)571-581
Number of pages11
JournalCell Host and Microbe
Volume14
Issue number5
DOIs
StatePublished - Nov 13 2013
Externally publishedYes

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Virology

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